A radiopharmaceutical-based method to investigate container-content interactions

3 October 2019

Dupire.C 1,2; Crauste-Manciet.S 1,3, Miguel.J 1,2, Bordenave.L 2, Fernandez.P 2,4, Debordeaux.F 1,2, Morgat.C 1,2,4
1 - Pharmaceutical technology department, Bordeaux University Hospital, France
2 - Nuclear medicine department, Bordeaux University Hospital, France
3 - ARNA ChemBioPharm U1212 INSERM - UMR 5320 CNRS, University of Bordeaux, France
4 - INCIA, UMR5287, University of Bordeaux, France

Container-content interactions may affect the quality and stability of various drugs. In this work we would propose a new methodology to anticipate adsorption and/or absorption mechanisms into/onto various materials based on the use of radiopharmaceuticals.

Materials and methods
Approved (18F-FDG, 123I-iobenguane) or investigational radiopharmaceuticals (68Ga-PSMA-617 and 68Ga-DOTANOC) were classified according to various physico-chemical parameters: molecular weight (MW), logP, logS and strongest basic pKa. Syringes (2mL, body in polypropylene (PP) and joint in polyethylene (PE)) and type I glass vial (15mL) with a polytetrafluoroethylene (PTFE) cap were first filled (n=3 for syringe and n=1 for vials and caps due to limited activity available) with a known activity of each radiopharmaceutical. Then, syringes and vials were emptied, and rinsed with an equal volume of NaCl 0.9%. After each step, the activity was quantified using a SPECT/CT (123I-iobenguane) or PET/CT camera (18F-FDG, 68Ga-PSMA-617 and 68Ga-DOTANOC).
Absorption (A) was quantified according to:
A = 100 x ((activity rinsed – background activity)/(activity full – background activity))
Adsorption (B) was quantified according to:
B = [100 x ((activity empty – background activity)/(activity full – background activity))] - A
Preliminary correlation studies were investigated to determine potential correlation between physico-chemical parameters and absorption/adsorption mechanisms

To develop prospective tool for interaction prediction we combined activity results to physico-chemical data. For example, with 123I-Iobenguane (MW = 271 Da; logP = 2.72; logS = -3,22; pkA = 11.27) in syringes, A and B were found at 9.27 ± 1.33 % and 16.55 ± 2.69 % respectively.
Taken together our results, MW was negatively correlated with adsorption on PP and PE (r = -0.6), with adsorption on glass (r = -0.8), with absorption and adsorption on PTFE (r = -0.6 and r = -0.8 respectively). LogP values were only positively correlated with absorption on PTFE (r = 0.8). LogS values were negatively correlated with absorption on PP and PE (r = -0.8) but were positively correlated with both adsorption on glass (r = 1.0) and PTFE (r = 1.0). Finally, pKa values were positively correlated with absorption on glass (r = 1.0), but negatively correlated with adsorption on glass (r = -1.0) and PTFE (r = -1.0).
Due to the limited number of samples studied, p-values were not presented.

Discussion - Conclusion
Our work would explore the possibility of using radiopharmaceuticals as an alternative method to quantify container-content interactions. Our preliminary results would support the feasibility of this approach. However, other radiopharmaceuticals should be investigated to strengthen our results and impact of excipients should also be studied. Our methodology might be extrapolated to other pharmacotechnical applications.

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